Easy Scale-up of Wurster Processes for Pellet Drug Layering and Taste Masking
This poster was presented at the EuPFI 2024 in Rotterdam by Glatt Pharmaceutical Services:
Introduction
➢Bitter tasting active pharmaceutical ingredients (API) for children require effective taste masking.
➢ Pellets are ideal dosage forms:
- A pre-defined dose of API can be applied by layering
- Small spherical particles, with uniform and smooth surface, and a narrow particle size distribution can be further coated with functional excipients [1] to achieve e.g. taste masking, enteric protection or the controlled release of the API in defined parts of the gastro-intestinal tract.
- Production of different dosages appropriate for children by adapting the amount of pellets to be filled into capsules or sachets is easily possible.
- Formulations of small-sized pellets offer a valuable base for increased compliance and improved age-appropriate dosage forms.
Objectives
➢Manufacturing processes for pellet layering and coating are often considered as challenging, especially the scale-up from development scale to pilot and production scale [2, 3].
➢In this work, a proven and established scale-up concept for pellet layering and coating applying the Wurster technology is presented.
Materials
➢The poorly soluble API was layered on CELLETS® 350, followed by a seal coat (HPMC) and a taste masking coat (EC / HPMC), using Glatt´s Wurster technology.
➢The process was developed at the 0.5 – 1 kg scale (GPCG 1 / 2 / 3, 6” or 7” Wurster), scaled-up to the 40 kg pilot scale in two trials (GPCG 60, 18” Wurster) and then to the final production scale of 190 kg (GPCG 60, 32” Wurster) in two trials.
➢Important scale-up parameters are
➢batch size (BS),
➢inlet air volume (IAV),
➢spray rate (SR),
➢temperatures (inlet air (IAT), product (PT), outlet air (OAT)),
➢and atomisation air pressure (AAP) [Figure 1].
➢Process parameters for the next process step were determined with a scale-up model equation, maintaining the inlet air velocity and evaporation capacity (product humidity) in the process [Table 1]. The final pellets were characterised for bulk density, residual moisture, yield, assay, [Table 2] dissolution [Figure 3], particle size [Figure 4] and ICH stability.
Scale-up concept – theory
Figure 1: Illustration of relevant process parameters and their scale-up-concept (batch size (BS), inlet air volume (IAV), spray rate (SR), inlet air temperature (IAT), product temperature (PT), outlet air temperature (OAT), and atomisation air pressure (AAP))
Scale-up concept – process parameters
Results
➢Two scale-up trials were performed in the 40 kg-pilot scale with yields of 98 – 99 %, assay values of 99 – 100 % and reproducible dissolution profiles within the specification.
➢The scale-up to the production batch size of 190 kg was performed in two trials with comparable results.
➢All batches were within specification; product stability was proven by ICH stability testing (data not shown).
➢Taste masking efficiency is demonstrated by dissolution testing in phosphate buffer pH 7,0 for 5 min (data not shown).
Conclusion
➢Taste masking of pellets by Wurster technology was successfully scaled-up to the production scale of 190 kg maintaining good yields, assay values and the intended dissolution profile.
➢Scale-up parameters for fluid bed processes can be efficiently pre-calculated.
➢The basis for scale-up and reliable processes in the production scale is a founded process development and optimisation in the development scale (e. g. 1 – 4 kg).
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Source: A. Grave; A. Rakotonirina | Glatt Pharmaceutical Services GmbH & Co. KG, Binzen, Germany, Poster “Easy Scale-up of Wurster Processes for Pellet Drug Layering and Taste Masking”
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